The objective of this project is to develop improved methods for studying the metabolism biologically significant materials through improved instrumental methods of microanalysis. Primary emphasis will be on chromatographic methods of separation, including gas-liquid, thin-layer, and liquid-liquid chromatography all used in conjunction with radioisotopes. Effort will be directed toward devising new GLC detectors that are specific for distinctive chemical groupings such as halogens, phosphorus, or nitrogen. Then these detection methods will be applied. The objective will be to develop more specific and sensitive methods of analysis not only for compounds that contain these specific groupings, but for others that can be labeled with these groupings by reaction with specific reagents. Effort will also be directed toward developingautomatic detection systems for thin-layer and liquid-liquid chromatography so that microanalysis using these methods can be more accurately and sensitively quantified. Mass spectrometry, in conjunction with GLC will be applied to the analysis of drugs and metabolites in serum. Effort will be directed toward development of the mass spectrometric system as a more sensitive and rapid method of analysis. The development of improved methods for studying the dynamics of the metabolism of lipids with radioisotopes will be undertaken, including methods for separating labeled compounds by various forms for chromatography, and for assaying the radio-activity in these compounds more accurately and conveniently.